Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Investigation of NADP-dependent aldehyde reductase activity in mouse liver led to the finding that two distinct reductases are separable by DE52 ion exchange chromatography. Aldehyde reductase I (AR I) appears in the effluent, while aldehyde reductase II (AR II) is eluted with a salt gradient. By several procedures AR II was purified over 1100-fold from liver supernatant fraction, but AR I could be pruified only 107-fold because of its instability. The two enzymes are different in regard to pH optimum, substrate specificity, response to inhibitors, and reactivity with antibody to AR II. While both enzymes utilize aromatic aldehydes well, only AR II ACTS ON D-glucuronate, indicating that it is the aldyhyde reductase recently reported to be identical to NADP-L-gulonate dehydrogenase. The presence of two NADP-linked aldehyde reductases in liver has apparently not heretofore been reported.
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PMID:Resolution and partial characterization of two aldehyde reductases of mammalian liver. 1 91

NADPH-dependent enzymatic reduction of aromatic aldehydes and ketones observed in the cytosol of guinea pig liver was mediated by at least three distinct reductases (AR 1, AR 2, and AR 3), which were separated by DEAE-cellulose chromatography. By several procedures AR 2 and AR 3 were purified to homogeneity, but AR 1 could be purified only 30-fold because of the small amount. These enzymes were found to have similar molecular weights of 34,000 to 36,000 and similar Stokes radii of about 2.5 nm. AR 3 was identical to aldehyde reductase [EC 1.1.1.2] in substrate specificity for aromatic aldehydes and D-glucuronate and specific inhibition by barbiturates. AR 1 and AR 2 acted on aromatic ketones and cyclohexanone as well as aromatic aldehydes at optimal pHs of 5.4 and 6.0, respectively, and were immunochemically distinguished from AR 3. AR 1 was the most sensitive to sulfhydryl reagents, and AR 2 was more stable at 50 degrees C than the other enzymes. Similar heterogeneity was observed in the kidney enzymes, but other tissues had little aldehyde reductase activity and contained only AR 3. In addition, lung contained a high molecular weight aromatic ketone reductase different from the above reductases.
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PMID:Purification and properties of reductases for aromatic aldehydes and ketones from guinea pig liver. 11 54

The pH dependence of steady-state parameters for aldehyde reduction and alcohol oxidation were determined in the human liver aldehyde reductase reaction. The maximum velocity of aldehyde reduction with NADPH or 3-acetyl pyridine adenine dinucleotide phosphate (3-APADPH) was pH independent at low pH but decreased at high pH with a pK of 8.9-9.6. The V/K for both nucleotides decreased below a pK of 5.7-6.2, as did the pKi of competitive inhibitors NADP and ATP-ribose, suggesting that the 2'-phosphate of the nucleotide has to be deprotonated for binding to the enzyme. The pK of the 2'-phosphate of NADPH appears to be perturbed in the ternary complexes to 5.2-5.4. The V/K for NADPH, the V/K for 3-APADPH, and the pKi of ATP-ribose also decreased above a pK of 9-10, suggesting interaction of the 2'-phosphate of the nucleotide with a protonated base, perhaps lysine. Since protonation of a residue with a pK of 8 (evident in V/K for DL-glyceraldehyde and V/K for L-gulonate versus pH profiles) appears to be essential for aldehyde reduction, and deprotonation for alcohol oxidation, this residue appears to act as a general acid-base catalyst. An additional anion binding site with a pK of 9.94 facilitates the binding of carboxylic substrates such as D-glucuronate. With NADPH as the coenzyme the primary deuterium isotope effects on V and V/K for NADPH were close to unity and pH independent, suggesting that the hydride transfer step is not rate determining over the experimental pH range. With 3-APADPH as the coenzyme, the maximum velocity, relative to NADPH was three- to four-fold lower. Isotope effects on V, V/K for 3-APADPH, and V/K for D-glucuronate were pH independent and equal to 2.2-2.8, indicating that the chemical step of the reaction is relatively insensitive to pH. These data suggest that substrates bind to both the protonated and the deprotonated forms of the enzyme, though only the protonated enzyme catalyzes aldehyde reduction and the deprotonated enzyme catalyzes alcohol oxidation. On the basis of these results a scheme for the chemical mechanism of aldehyde reductase is postulated.
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PMID:Human liver aldehyde reductase: pH dependence of steady-state kinetic parameters. 165 14

3-Deoxyglucosone reductase activity in the extracts of rat, pig and human livers was potently inhibited by aldehyde reductase inhibitors. The major species of 3-deoxyglucosone reductase purified from human and pig livers were biochemically and immunochemically identical with aldehyde reductase. The two enzymes and rat liver aldehyde reductase exhibited higher catalytic efficiency for 3-deoxyglucosone than for D-glucuronate, a representative substrate of aldehyde reductase.
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PMID:Aldehyde reductase is a major protein associated with 3-deoxyglucosone reductase activity in rat, pig and human livers. 195 87

Osmoregulation in inner medullary cells depends in part on cellular accumulation of sorbitol, the production of which from glucose is catalyzed by aldose reductase. To identify nephron segments that contain aldose reductase, we developed a fluorometric ultramicroassay to measure aldose reductase activity in microdissected nephron segments from collagenase-treated kidneys of Sprague-Dawley rats. DL-Glyceraldehyde (10 mM) was used as a substrate. Substantial aldose reductase activities were found in all three inner medullary renal tubule segments: thin descending limbs, thin ascending limbs, and inner medullary collecting ducts. Activity increased with depth into the inner medulla in all three segments. When aldose reductase activities were normalized by cell volume the activities in the three inner medullary segments were similar. Little or no aldose reductase activity was measured in glomeruli or any cortical or outer medullary nephron segment. Both proximal convoluted and proximal straight tubules were found to have a substantial capacity to reduce DL-glyceraldehyde, but the finding of greater reductase activity with D-glucuronate (10 mM) than with D-xylose (10 mM) indicated that the activity was due to aldehyde reductase. Sorbitol dehydrogenase (measured by a similar ultramicroassay method) was present in substantial amounts in proximal tubules, but not in inner medullary collecting ducts. The overall pattern of enzyme activities is consistent with the proposed osmoregulatory role for sorbitol in all three inner medullary renal tubule segments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aldose reductase activities in microdissected rat renal tubule segments. 249 37

Two major and two minor forms of dihydrodiol dehydrogenase with similar molecular weights of around 36000 were purified from monkey liver cytosol. All the forms oxidized trans-dihydrodiols of benzene and naphthalene and reduced aromatic aldehydes, but showed differences in charge, specificity for other substrates and inhibitor sensitivity. One major (pI 8.7) and one minor (pI 7.9) form of the enzyme exhibited high activity for alicyclic alcohols and sensitivity to o-phenanthroline. The other major form (pI 6.2) oxidized 3 alpha-hydroxysteroids and was inhibited by dexamethasone and indomethacin, whereas the other minor form (pI 5.8) showed high reductase activity for aldehydes including D-glucuronate and sensitivity to barbital and sorbinil, and cross-reacted with human aldehyde reductase. The results indicate that the multiple forms of monkey liver dihydrodiol dehydrogenase are indanol dehydrogenases, 3 alpha-hydroxysteroid dehydrogenase and aldehyde reductase.
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PMID:Purification and properties of multiple forms of dihydrodiol dehydrogenase from monkey liver. 269 60

Eye MAO-A, MAO-B, semicarbazide-sensitive amine oxidase (SSAO) and aldehyde reductase (AR) activities were measured in young and old rats. When enzyme activity is expressed as nmol (mg protein)-1 min-1, a significant decrease (18-23%) of SSAO activity in the eye of old rats was found, whereas there was no significant difference in MAO-A and MAO-B activities. A significant increase of AR activity with D-xylose (67%), DL-glyceraldehyde (64%), D-glucuronate (43%) and D-glucose (21%) was found in the eye of old rats. These results suggest that changes in the activities of the amine metabolizing enzymes of rat eye with age might have consequences for their function in senescence; particularly, the increase of AR activity might be involved in cataract formation.
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PMID:Age-related changes in the activities of the amine metabolizing enzymes of rat eye. 286 49

Aldehyde reductase (AR) activity was measured in whole brain, different brain areas, kidney and duodenum of 23-26 months old rats and then compared to matched animals of 3 months. No significant changes in AR activity were found in whole brain of old rats with D-glucose as substrate. A significant increase in AR activity in old rats was found in striatum (12%), cerebellum (26%), midbrain (6%), brainstem (19%) and hypothalamus (13%) with p-nitrobenzaldehyde, in striatum (14%), midbrain (10%), brainstem (52%), hypothalamus (9%) and hippocampus (20%) with D-glucuronate, in cerebellum (21%) with D-xylose, in striatum (43%), cerebellum (19%) and brainstem (22%) with DL-glyceraldehyde, and in brainstem (15%) with pyridine 3-aldehyde. A significant decrease in AR activity in old rats was found in midbrain (16%), brainstem (19%) and hypothalamus (19%) with D-xylose, and in midbrain (13%) with DL-glyceraldehyde. A significant decrease in AR activity in old rats was found in kidney with p-nitrobenzaldehyde (30%), D-xylose (31%), DL-glyceraldehyde (33%), pyridine 3-aldehyde (27%) and in duodenum with p-nitrobenzaldehyde (21%), but a significant increase was found in duodenum with pyridine 3-aldehyde (29%). Preliminary experiments show an increase (42%) of sorbitol dehydrogenase activity in whole brain of old rats. The present results clearly indicate that the AR activity increase in the brain of old rats is the high-Km form of aldehyde reductase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Further investigation on aldehyde reductase activity in ageing rat tissues. 286 49

The kinetic mechanism of the major sheep liver aldehyde reductase (ALR1) was studied with three aldehyde substrates: p-nitrobenzaldehyde, pyridine-3-aldehyde and D-glucuronate. In each case the enzyme mechanism was sequential and product-inhibition studies were consistent with an ordered Bi Bi mechanism, with the coenzymes binding to the free enzyme. Binding studies were used to investigate the interactions of substrates, products and inhibitors with the free enzyme. These provided evidence for the binding of D-glucuronate, L-gulonate and valproate, as well as NADP+ and NADPH. The enzyme was inhibited by high concentrations of D-glucuronate in a non-competitive manner, indicating that this substrate was able to bind to the free enzyme and to the E X NADP+ complex at elevated concentrations. Although the enzyme was inhibited by high pyridine-3-aldehyde concentrations, there was no evidence for the binding of this substrate to the free enzyme. Sheep liver ALR1 was inhibited by the ionized forms of alrestatin, sorbinil, valproate, 2-ethylhexanoate and phenobarbitone, indicating the presence of an anion-binding site similar to that described for the pig liver enzyme, which interacts with inhibitors and substrates containing a carboxy group. Sorbinil, valproate and 2-ethylhexanoate inhibited the enzyme uncompetitively at low concentrations and non-competitively at high concentrations, whereas phenobarbitone and alrestatin were non-competitive and uncompetitive inhibitors respectively. The significance of these results with respect to inhibitor and substrate binding is discussed.
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PMID:Kinetic mechanism of sheep liver NADPH-dependent aldehyde reductase. 359 33

An aldehyde reductase catalyzing the NADPH-dependent reduction of D-erythrose 4-phosphate to D-erythritol 4-phosphate was purified from beef liver. It was proved to be homogeneous by polyacrylamide gel electrophoresis, sodium dodecyl sulfate polyacrylamide gel electrophoresis and ultracentrifugation analysis. The enzyme was proved to be a monomeric enzyme and its molecular weight was about 40,000. The enzyme was able to reduce not only tetroses but also trioses, aromatic aldehydes, D-glucuronate and succinic semialdehyde. Apparent Km-values for aromatic aldehydes were lower than those for tetroses, trioses, D-glucuronate and succinic semi-aldehyde. Barbiturates and valproate were potent inhibitors of the enzyme and their apparent K1-values were in the range of 80-180 microM. Quercitrin was the most potent inhibitor and its K1-value was about 7 microM. From the viewpoint of substrate specificity and inhibitor sensitivity, it seems that the enzyme belongs to the high-Km type aldehyde reductases.
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PMID:Purification and properties of beef liver aldehyde reductase catalyzing the reduction of D-erythrose 4-phosphate. 388 76


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